Evaluating the impact of soy compounds on breast cancer using the data mining approach.

Accumulating evidence has shown that soy intake is associated with the promotion of health and prevention of cancers. However, the relationship between the intake of soy compounds and the risk of breast cancer is still debatable. In this study, we use mathematical models for assessing the impact of soy phytoestrogens and protein/peptide intervention on breast cancer development using the datasets acquired from a large number of published studies. We used data mining models, including the decision tree classification and association rule methods, to analyze 478 data collected from 201 research papers. The results indicated that the intervention of soy proteins and peptides, especially lunasin (LUN) and bowman-birk protease inhibitor (BBI), has a positive impact on different types of breast cancer, while the effects of soy phytoestrogens are inconsistent in breast cancer development. Among soy phytoestrogens, daidzein (DAI) exhibited the highest negative impact on breast cancer, followed by coumestrol (COU), soysapogenol (SAP), genistein (GEN), and equol (EQ). With regard to the type of cancer, phytoestrogens should be carefully considered in estrogen receptor (ER)+ or progesterone receptor (PR)+ breast cancer. In the case of ER-, PR- or triple negative type, both soy categories can be used as auxiliary interventions. In summary, this is the first study to use data mining to explore the relationship between the intake of soy phytoestrogens or proteins/peptides and breast cancer development. Our findings indicate that soy intervention might reduce breast cancer development. However, the specific soy compound and cancer type should be considered before allocating a precise nutrient intervention.

Updating the research on the chemopreventive and therapeutic role of the peptide lunasin.

Chronic diseases have become the medical challenge of the 21st century because of their high incidence and mortality rates. Modulation of diet and lifestyle habits is considered as the best strategy for the prevention of these disorders. Health promoting benefits beyond their nutritional effects have been described for multiple dietary compounds. Among these compounds, the peptide lunasin is considered as one of the most promising. Naturally present in soybean, lunasin has been extensively studied in the last two decades because of its potential against chronic diseases such as cancer, cardiovascular and immunological disorders. The purpose of this article is to summarise the evidence on the presence of lunasin in soybean and derived foods, and its bioavailability once it is orally ingested. The protective and therapeutic effects of this peptide against cancer, oxidative stress, inflammation, and high cholesterol levels as well as the molecular mechanisms of action involved in these effects are also described in this review. © 2017 Society of Chemical Industry.

Chemopreventive role of food-derived proteins and peptides: A review.

Cancer is one of the leading causes of mortality and disability worldwide. Although great advances in cancer treatments such as chemotherapy, surgery, and radiation are currently being achieved, their application is associated with numerous and expensive adverse side effects. Epidemiological evidence has demonstrated that the consumption of certain foods potentially prevents up to 35% of cancer cases. Bioactive components are ubiquitous in nature, also in dietary food, providing an essential link in health maintenance, promotion, and prevention of chronic diseases, such as cancer. Development of bioactive proteins and peptides is a current and innovative strategy for cancer prevention/cure. A growing body of anticancer protein and peptides from natural sources has shown the ability to reduce tumor progression through multiple mechanisms including apoptotic, antiproliferative, antiangiogenic, and immunomodulatory activities. This review is focused on proteins and peptides from different food sources including plants, milk, egg, and marine organisms in which chemopreventive properties have been demonstrated. Other aspects such as mechanism of action, bioavailability, and identification and characterization of food-derived peptides by advance separated technologies are also included. This review highlights the potential application of food-derived peptides as functional food ingredients and pharmaceutical candidates in the auxiliary therapy of cancer.

Triterpenoids and Polysaccharide Fractions of Ganoderma tsugae Exert Different Effects on Antiallergic Activities.

This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (Gt-PS) extracts from Ganoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL-) 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4(+) T cells cultures also confirmed that Gt-TRE (5 ~ 50 µg/mL) significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN)-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL) and significantly suppressed IFNγ secretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264.7 cells and transfected EL4 cells. IL-4 secreted by this transfected EL-4 cells was also significantly decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may exert different effects on NF-κB related cytokines expression. These data suggested that triterpenoids fraction of Ganoderma tsugae might be the main constituents to alleviate allergic asthma.

Dietary factors regulate cytokines in murine models of systemic lupus erythematosus.

Cytokines play the active roles in the pathogenesis of systemic lupus erythematosus (SLE) and contribute significantly to the immune imbalance in this disease. Conservative therapeutic approaches, such as dietary modifications have been shown to have some beneficial impact on the disease activity of the SLE. Over the past years, accumulating evidences have supported a major role for specific dietary factors, including calorie restriction, n-3/n-6 fatty acids, vitamin A, vitamin D, vitamin E, phytoestrogens or herbal medicine in the regulation of cytokines involved in SLE development. Although there are many reviews that discuss the issue of nutrition and immunity, there are relatively few articles that focus on the regulation of cytokines by dietary factors. This concise review will summarize those animal studies that investigated not only the outcome of autoantibody production and proteinuria, but also cytokines production. However, the field of dietary factors in the immunomodulation of SLE is still in its infancy. More clinical studies are needed to confirm the preliminary results and advance the knowledge in this field. Lifestyle modification and adjustments in diet are important and encouraged to be suggested as an adjuvant therapy for SLE.

Lunasin and Bowman-Birk protease inhibitor concentrations of protein extracts from enzyme-assisted aqueous extraction of soybeans.

Lunasin and Bowman-Birk protease inhibitor (BBI) are two soybean peptides to which health-promoting properties have been attributed. Concentrations of these peptides were determined in skim fractions produced by enzyme-assisted aqueous extraction processing (EAEP) of extruded full-fat soybean flakes (an alternative to extracting oil from soybeans with hexane) and compared with similar extracts from hexane-defatted soybean meal. Oil and protein were extracted by using countercurrent two-stage EAEP of soybeans at 1:6 solids-to-liquid ratio, 50 °C, pH 9.0, and 120 rpm for 1 h. Protein-rich skim fractions were produced from extruded full-fat soybean flakes using different enzyme strategies in EAEP: 0.5% protease (wt/g extruded flakes) used in both extraction stages; 0.5% protease used only in the second extraction stage; no enzyme used in either extraction stage. Countercurrent two-stage protein extraction of air-desolventized, hexane-defatted soybean flakes was used as a control. Protein extraction yields increased from 66% to 89-96% when using countercurrent two-stage EAEP with extruded full-fat flakes compared to 85% when using countercurrent two-stage protein extraction of air-desolventized, hexane-defatted soybean flakes. Extruding full-fat soybean flakes reduced BBI activity. Enzymatic hydrolysis reduced BBI contents of EAEP skims. Lunasin, however, was more resistant to both enzymatic hydrolysis and heat denaturation. Although using enzymes in both EAEP extraction stages yielded the highest protein and oil extractions, reducing enzyme use to only the second stage preserved much of the BBI and Lunasin.

Lunasin, a novel seed peptide for cancer prevention.

Carcinogenesis is a multistage process derived from a combination of multiple heritable and environmental factors. It has been reported that populations consuming high levels of soybean products have both lower cancer incidence and mortality rates in the western countries. Lunasin is a novel and promising peptide initially discovered in soy and now found in wheat, barley and other seeds. Its cancer-preventive efficacy has been shown in mammalian cells which were induced by chemical carcinogens and viral oncogenes. Moreover, this peptide has been found to prevent skin cancer in a mouse cancer model induced by chemical carcinogens. Its bioavailability after oral administration makes it a perfect candidate as a chemopreventive agent. The purpose of this article is to review the discovery of this seed peptide and the most recent evidence on its possible benefits as an anticancer agent.

Low and high levels of alpha-tocopherol exert opposite effects on IL-2 possibly through the modulation of PPAR-gamma, IkappaBalpha, and apoptotic pathway in activated splenocytes.

OBJECTIVE: We previously demonstrated that a high dose of alpha-tocopheryl succinate inhibits interleukin-2 (IL-2) mRNA and production in autoimmune-prone MRL/lpr mice. In the present study, we investigated the regulation of alpha-tocopherol (alphaTOC) on IL-2 gene expression by examining the mRNA of IL-2, inhibitor kappaBalpha (IkappaBalpha), and peroxisome proliferator-activated receptor-gamma (PPARgamma). METHODS: Messenger RNA expression in active splenocytes of BALB/c mice was investigated with reverse transcriptase polymerase chain reaction. RESULTS: Levels of IL-2 mRNA in phorbol 12-myristate 13-acetate/ionomycin activated splenocytes and cytokine in T-helper-1 cells were increased by 50 microM of alphaTOC but decreased by 1 mM of alphaTOC. In addition, the IkappaBalpha gene expression significantly increased by the high dose (>or=500 microM) of alphaTOC, suggesting an inhibition on nuclear factor-kappaB pathway for activation of IL-2 expression. PPARgamma mRNA level in activated splenocytes was upregulated by 1 mM of alphaTOC. PPARgamma mRNA level in unstimulated splenocytes was upregulated by alphaTOC in a dose-dependent manner, suggesting that alphaTOC might enhance the PPARgamma signaling pathway. High-dose alphaTOC induced apoptosis of splenocytes and inhibited phytohemagglutinin-stimulated T-cell proliferation. Conversely, the proliferative response of splenocytes was enhanced by 5 microM of alphaTOC. Low-dose (50 microM) alphaTOC increased IL-2 expression, which may have been due to the absence of downregulation of PPARgamma and IkappaBalpha on the IL-2 gene. CONCLUSION: The results indicated that low and high doses of alphaTOC exert opposite effects on IL-2, possibly through modulation of PPARgamma, IkappaBalpha, and apoptosis pathways. The present findings support our previous observation of opposite effects of low- and high-dose vitamin E on survival of MRL/lpr mice.

Opposite effects of low and high dose supplementation of vitamin E on survival of MRL/lpr mice.

OBJECTIVE: The purpose of this study is to investigate the effects of vitamin E supplementation on the autoimmune disease course in MRL/lymphoproliferative mice. METHODS: Three-month-old MRL/lymphoproliferative lpr female mice were fed an AIN-76 diet containing 50 mg/kg (control), 250 mg/kg (E5), 375 mg/kg (E7.5), or 500 mg/kg (E10) all-rac-alpha-tocopheryl acetate. Eight mice per group were killed for analysis after two months of experimental diets, and the rest of the mice were followed up to observe their proteinuria levels and life span. RESULTS: The data suggest that the life span of the E5 group was longer than the E10 group. Though alpha-tocopherol content in the plasma, liver, and kidneys increased in the mice fed the diet supplemented with vitamin E, the thiobarbituric acid reactive substance values in the liver and kidneys among these groups were not significantly different. IgM anti-ds-DNA and anticardiolipin antibodies were significantly higher in the E10 group than in those of the other groups. Phytohemagglutinin-stimulated interleukin (IL)-2 secretion was significantly lower, but concanavalinA-stimulated IL-4 and IL-10 production was significantly higher in the E10 group compared with the control group. The in vitro study also showed decreased IL-2 secretion and messenger RNA expression in phytohemagglutinin-stimulated splenocytes cultured in medium supplemented with high doses of vitamin E, but increased IL-2 with low doses of vitamin E. CONCLUSIONS: Our data suggest that low and high dose supplementation of vitamin E has the opposite effect on the survival of MRL/lpr mice. The inhibitory effect of Th1 from high vitamin E content may not be beneficial for those suffering from Th2 prone autoimmune diseases, such as systemic lupus erythematosus.

The effects of vitamin E supplementation on autoimmune-prone New Zealand black x New Zealand white F1 mice fed an oxidised oil diet.

The purpose of the present study was to investigate the effect of vitamin E supplementation on autoimmune disease in New Zealand blackxNew Zealand white F1 (NZB/W F1) female mice fed an oxidised oil diet. First, 5-month-old mice were fed an AIN-76 diet containing either 150 g fresh soyabean oil/kg (15S), 50 g fresh soyabean oil/kg + 100 g oxidised frying oil/kg (5S10F) or 5S10F supplemented with all-rac-alpha-tocopheryl acetate at 275 mg/kg diet level (5S10F5E) or 550 mg/kg (5S10F10E), respectively, in experiment 1. The results showed that mice fed the 5S10F10E diet had a lower anti-double-stranded DNA IgG antibody level and a longer lifespan than those fed the 15S and 5S10F diets. Therefore, the 5S10F and 5S10F10E treatments were repeated in experiment 2 for further analysis. The results showed that vitamin E supplementation in the oxidised oil significantly decreased thiobarbituric acid-reactive substance values in the kidney and spleen of NZB/W F1 mice. Interferon-gamma and IL-6 production by mitogen-stimulated splenocytes decreased in mice fed the 5S10F10E diet, whereas the secretion of IL-2 and IL-10 was not affected. The percentage of T-cells was significantly higher and that of MHC class II-bearing cells was lower in the spleens of the 5S10F10E group. The 5S10F10E group had a significantly higher linoleic acid (18 : 2n-6) composition than the 5S10F diet group. Therefore, vitamin E supplementation in oxidised oil might decrease oxidative stress, anti-double-stranded DNA IgG antibody, regulate cytokines and lymphocyte subsets, and subsequently alleviate the severity of autoimmune disease such as systemic lupus erythematosus under oxidative stress.